MANF调节小鼠脾脏巨噬细胞的分化。,Immunology Letters

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MANF调节小鼠脾脏巨噬细胞的分化。
Immunology Letters ( IF 3.3 ) Pub Date : 2019-06-19 , DOI: 10.1016/j.imlet.2019.06.007
Chao Hou ₁ , Dong Wang ₁ , Xiang Li ₁ , Yufeng He ₁ , Chuansheng Wei ₁ , Rong Jiang ₂ , Jun Liu ₁ , Lijie Feng ₁ , Yuxian Shen ₁

Affiliation

脾脏免疫细胞，特别是巨噬细胞，在多种病理过程中起关键作用。业已证明，中脑星形胶质细胞源性神经营养因子（MANF）具有抗炎和免疫调节的功能，在生理和病理生理情况下，MANF如何影响脾脏免疫细胞仍是未知的。在这项研究中，我们构建了单巨噬细胞特异性MANF基因敲除（MøMANF-/-）小鼠，发现脾M1巨噬细胞增加，但与野生型（WT）小鼠相比，脾形态和大小没有明显变化。此外，我们建立了四氯化碳（CCl4）诱导的肝纤维化的病理生理情况。在肝纤维化下，MøMANF-/-小鼠脾脏M2巨噬细胞和CD138 +浆细胞显着增加。一致地，我们还发现MøMANF-/-小鼠的血清和脾脏中TGF-β1水平升高。在正常和肝纤维化条件下，单巨噬细胞特异性MANF基因敲除均不影响脾脏T和B细胞的数量。我们的结果表明，MANF对脾脏免疫细胞有明显的调节作用，而MANF对脾脏巨噬细胞的分化有特殊的调节作用，这可能对脾脏的生理和病理生理过程产生重大影响。

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MANF regulates splenic macrophage differentiation in mice.

Splenic immune cells, especially macrophages, play a key role in multiple pathological processes. With a proved anti-inflammatory and immunoregulatory function of mesencephalicastrocyte-derived neurotrophic factor (MANF) in inflammatory disorders, how MANF affects splenic immune cells in physiological and pathophysiological situations is still unknown. In this study, we constructed mono-macrophage-specific MANF knockout (Mø MANF-/-) mice and found the increased splenic M1 macrophages, but no significant change of splenic morphology and size compared with wild type (WT) mice. Also, we established the pathophysiological situation of carbon tetrachloride (CCl4)-induced hepatic fibrosis. Under the hepatic fibrosis, splenic M2 macrophages and CD138+ plasma cells were significantly increased in Mø MANF-/- mice. Consistently, we found the increased TGF-β1 level in serum and spleen of Mø MANF-/- mice as well. Mono-macrophage-specific MANF knockout did not affect the number of splenic T and B cells under both the normal and hepatic fibrosis conditions. Our results suggest a distinct regulation of MANF on splenic immune cells and a specific regulation of MANF on the differentiation of splenic macrophages, which may exert a significant impact on physiological and pathophysiological processes of the spleen.

更新日期：2019-11-01

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